InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BCL6

Summary

InnateDB Protein

IDBP-293546.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BCL6

Protein Name

B-cell CLL/lymphoma 6

Synonyms

BCL5; BCL6A; LAZ3; ZBTB27; ZNF51;

Species

Homo sapiens

Ensembl Protein

ENSP00000384371

InnateDB Gene

IDBG-69349 (BCL6)

Protein Structure

UniProt Annotation

Function

Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6- binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53- dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH- dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation. {ECO:0000269PubMed:10981963, ECO:0000269PubMed:12402037, ECO:0000269PubMed:12414651, ECO:0000269PubMed:12504096, ECO:0000269PubMed:15454082, ECO:0000269PubMed:15577913, ECO:0000269PubMed:16142238, ECO:0000269PubMed:17828269, ECO:0000269PubMed:18212045, ECO:0000269PubMed:18280243, ECO:0000269PubMed:22113614, ECO:0000269PubMed:23166356, ECO:0000269PubMed:23911289, ECO:0000269PubMed:9649500}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:12504096, ECO:0000269PubMed:17828269, ECO:0000269PubMed:22113614, ECO:0000269PubMed:23166356}.

Disease Associations

Note=Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain. Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region. Translocation t(3;6)(q27;p21) with Histone H4. Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1.Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.

Tissue Specificity

Expressed in germinal center T- and B-cells and in primary immature dendritic cells. {ECO:0000269PubMed:10981963, ECO:0000269PubMed:12402037, ECO:0000269PubMed:15454082, ECO:0000269PubMed:16142238, ECO:0000269PubMed:16455075, ECO:0000269PubMed:17828269, ECO:0000269PubMed:18212045, ECO:0000269PubMed:9649500}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 201 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	201 [view]
Protein-Protein	151 [view]
Protein-DNA	48 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding
GO:0001227	RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0031490	chromatin DNA binding
GO:0043565	sequence-specific DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0000060	protein import into nucleus, translocation
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000902	cell morphogenesis
GO:0001953	negative regulation of cell-matrix adhesion
GO:0002467	germinal center formation
GO:0002634	regulation of germinal center formation
GO:0002829	negative regulation of type 2 immune response
GO:0002903	negative regulation of B cell apoptotic process
GO:0006351	transcription, DNA-templated
GO:0006954	inflammatory response
GO:0006974	cellular response to DNA damage stimulus
GO:0007266	Rho protein signal transduction
GO:0007283	spermatogenesis
GO:0008104	protein localization
GO:0008285	negative regulation of cell proliferation
GO:0030036	actin cytoskeleton organization
GO:0030183	B cell differentiation
GO:0030308	negative regulation of cell growth
GO:0030890	positive regulation of B cell proliferation
GO:0032319	regulation of Rho GTPase activity
GO:0032764	negative regulation of mast cell cytokine production
GO:0035024	negative regulation of Rho protein signal transduction
GO:0042092	type 2 immune response
GO:0042127	regulation of cell proliferation
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043380	regulation of memory T cell differentiation
GO:0045596	negative regulation of cell differentiation
GO:0045629	negative regulation of T-helper 2 cell differentiation
GO:0045892	negative regulation of transcription, DNA-templated
GO:0048294	negative regulation of isotype switching to IgE isotypes
GO:0048821	erythrocyte development
GO:0050727	regulation of inflammatory response
GO:0050776	regulation of immune response
GO:0051272	positive regulation of cellular component movement